1. Technical Field
The present invention relates to benzylamine analogues, pharmacologically acceptable salts or esters thereof and pharmaceutical compositions containing the same that have superior acetylcholinesterase inhibitory action and selective serotonin reuptake inhibitory action, and which are useful as therapeutic or prophylactic drugs for Alzheimer's disease, depression, Huntington's chorea, Pick's disease, tardive dyskinesia, compulsive disorders or panic disorders.
2. Background Art
Given the rapid growth of the elderly population, there is an urgent desire for the establishment of a treatment method for senile dementia as typified by Alzheimer's disease, and research and development is being conducted on therapeutic drugs for Alzheimer's disease from various perspectives. Since decreased acetylcholine concentration in the brain and decreased cholinergic function are observed in Alzheimer's disease patients, studies have been conducted on the treatment of Alzheimer's disease using acetylcholine precursor compounds, acetylcholinesterase inhibitors and acetylcholine agonists for the purpose of activating cholinergic function. Activation of the central cholinergic nervous system has been demonstrated to be effective for the treatment of mild to moderate cases of Alzheimer's disease by clinical application of acetylcholinesterase inhibitors (Rev. Contemp. Pharmacother., 6, 335 (1995)). Serious adverse side effects, namely liver toxicity, which were observed with early acetylcholinesterase inhibitors, have been improved considerably by ensuring inhibitory action specificity of the compounds to acetylcholinesterase and butylcholinesterase, and second generation acetylcholinesterase inhibitors are currently being developed (Neurology, 50, 136 (1998)).
Depression is frequently reported as a peripheral symptom in early Alzheimer's disease patients. Treatment using antidepressants has been tried, based on the idea -that while impairment of cognitive function is still mild, core symptoms such as cognitive function can be expected to be improved by alleviating the depression (Ann. N.Y. Acad. Sci., 695, 254 (1993)). At present, the brain's serotonin system is widely recognized to be involved in depression. Research is being conducted on drugs that act on serotonin receptors or serotonin reuptake inhibitors, and selective serotonin reuptake inhibitors have been reported to be antidepressants having minimal adverse side effects (Drugs, 32, 481 (1986)). Drugs that are provided with both acetylcholinesterase inhibitory action and selective serotonin reuptake inhibitor action are expected to be able to alleviate depression and improve cognitive function, which are the core symptoms of Alzheimer's disease, and are thought to be more effective therapeutic-drugs for Alzheimer's disease than compounds only having acetylcholinesterase inhibitory action. However, compounds having a similar chemical structure to the compounds of the present invention that also have both acetylcholinesterase inhibitory action and selective serotonin reuptake inhibitory action have heretofore not been known.